Rapid production systems currently employed with respect to cattle, sheep and other domestic ruminants typically entail intensive use of relatively expensive high energy feedstuffs to maximize growth rates. Examples include any feedstuffs having a high starch content or a high percentage of total digestive nutrients (TDN). Usually, these feedstuffs contain relatively large quantities of grain or other finely ground energy and protein sources. Although these feedstuffs are almost always high in potential energy content, they differ substantially in fiber content from the grasses, roughage and other forages which it is generally believed ruminants evolved to consume.
As a result, stresses are created in the digestive tracts of ruminants which are maintained on relatively high energy, low fiber diets. The nature and collective age of the microbial population which exists in the rumen in a symbiotic relationship with the animal can be detrimentally altered, leading to increased production of volatile fatty acids and a subsequent increase in systemic acid load. In severe cases, these stresses can lead to acute digestive dysfunctions, such as acidosis, displaced abomasum and other pathological conditions. However, even in mild, subclinical cases, these stresses decrease the efficiencies with which ruminants digest and utilize high energy feedstuffs. Ultimately, inefficiencies are created in the overall production system, and they are compounded by both the expense of underutilized, high energy or high protein feedstuffs and the cost where veterinary or other corrective treatment is required.
Insufficient salivation, brought about by the relatively minimal chewing necessary to consume fine particulate, high energy feedstuffs has previously been recognized as a primary cause of many of these disorders. It has been reported that saliva is the source of up to 70% of the total water flux through the rumen as well as the principal source of ruminal buffering agents. Additionally, it is known that high energy diets promote increased production of volatile fatty acids. Thus, animal scientists have recognized that a significant decrease in ruminant salivation can lead to excess acidity, decreased digesta flow to the small intestine, a slower rate at which dietary nutrients are washed out of the rumen into the small intestine and an alteration in the nature and collective age of the microbial population which exists in the rumen in symbiosis with the host animal.
Heretofore, practical efforts to address the problems arising from feeding ruminants a high energy diet have tended toward treatment of symptoms rather than finding cures or true preventatives. In large part, these efforts have focused upon increasing the fiber content of feedstuffs or upon supplementing high energy diets with salts, minerals or buffering agents such as sodium chloride, calcium chloride, limestone, various bicarbonates and bentonites. While these measures have been of some assistance in enhancing rumen digesta turnover and in controlling excess acidity as well as some of the other digestive dysfunctions associated with high grain diets, they have been substantially less than completely successful.
It is known that, by stimulating the exocrine glands, certain parasympathomimetic compounds significantly enhance salivation and pancreatic fluid secretion in ruminants and other animals. However, these compounds have been subject to a lack of reliable information and predictability regarding the amount of salivation they induce and as to whether they can be administered repeatedly to animals over a prolonged period. Additionally, these compounds have been reported to produce other undesirable effects, such as diarrhea, increased urination and decreased heart and respiratory rates. Some of these compounds have been reported to be toxic and have been the subject of significant efforts to purify certain feedstuffs. Thus, prior to this invention, parasympathomimetic compounds had not been adopted for maintaining any animals on any diet.
Slaframine, one of the naturally occurring indolizine alkaloids produced by the fungus Rhizoctonia leguminicola, is a parasympathomimetic compound which is known to cause increased salivation. In the Midwest and elsewhere in the 1950's, 1960's and 1970's, there were periodic outbreaks among cattle and other livestock of salivary syndrome or "slobbers". Typically, the livestock showed pathologic symptoms such as excessive salivation, decreased feed intake, abortion, diarrhea, lacrimation and behavioral changes. In some instances, the livestock died.
"Slobbers" was traced to consumption by the livestock of red clover hay containing the fungus, Rhizoctonia leguminicola. Slaframine, was reported to be the causative factor and was subsequently reported to be a toxin. More recently, however, it has been discovered that swainsonine (1,2,8-trihydroxyoctahydroindolizine), another compound co-produced with slaframine by Rhizoctonia leguminicola, is the active toxin produced by that fungus.
We have discovered that low level dosages of purified slaframine (i.e., slaframine in the absence of significant quantities of swainsonine) can be administered to cattle and other ruminants over prolonged periods of time so as to increase rumen digesta turnover rates and alter a variety of other rumen parameters in ways which are quite beneficial to livestock maintained on relatively high energy, low fiber diets. Moreover, we have discovered that, when administered to ruminants in accordance with this invention, slaframine does not produce pathological conditions.